Recent attempts to understand the dynamic contributions of genes and environments to human development have emphasized the need to consider environments at different scales;the simplest such distinction is between the immediate home environment and the more distal influences of school, neighborhood, socioeconomics and culture. Rodent species have proved powerful models for investigating the role of these more proximal processes, namely maternal care, on the development of brains and behavior. The examination of how parental care interacts with more distal influences, however, has largely been limited to correlational studies in humans and manipulative studies in non-human primates. Although both sources of data are important, neither provides the capacity for neuronal manipulation present in rodent models. We propose to extend rodent neuroscience into semi-natural settings using a novel combination of gene therapy, RNA interference (RNAi), radiotelemetry and focal video sampling. We outline a research plan that would do so with a unique rodent species, the prairie vole, known for its pairbonding and bi-parental care. We propose to use RNAi methods to manipulate the expression of the vasopressin 1a receptor (V1aR) in the ventral pallidum, a brain area necessary for male pairbonding. We propose to place males with reduced V1aR (V1Ai), control (CONT) males, and unmanipulated females in semi-natural enclosures, with different frequencies of V1Ai and CONT males forming different "neighborhoods." We will then examine the relationship between paternal V1Ai phenotype, social neighborhood, and the parental care received by young. Lastly, we will examine offspring from these nests on measures of stress reactivity, a well-characterized phenotype shaped by parental care in rodents, humans and non-human primates. The resulting data will uniquely address the reciprocal influences of proximal and distal environments on neural and behavioral outcomes. No less importantly, the study will develop methods that address how genomes and social environments interact to influence a broad range of phenotypes. PUBLIC HEALTH RELEVANCE: The interactions between children and their caregivers are critical to child development. Work on rodents has clarified the neuronal and hormonal mechanisms through which care can be translated into lifelong changes in physiology and behavior, including susceptibility to obesity, heart disease and depression. We propose to develop a unique combination of molecular and behavioral tools that would allow researchers to address more complex interactions between social environment, gene expression, and neurobiological and behavioral development.